An active tethering mechanism controls the fate of vesicles

Seong J. An, Felix Rivera-Molina, Alexander Anneken, Zhiqun Xi, Brian McNellis, Vladimir I. Polejaev and Derek Toomre ()
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Seong J. An: Yale University School of Medicine
Felix Rivera-Molina: Yale University School of Medicine
Alexander Anneken: Yale University School of Medicine
Zhiqun Xi: Yale University School of Medicine
Brian McNellis: Yale University School of Medicine
Vladimir I. Polejaev: Yale University School of Medicine
Derek Toomre: Yale University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Vesicle tethers are thought to underpin the efficiency of intracellular fusion by bridging vesicles to their target membranes. However, the interplay between tethering and fusion has remained enigmatic. Here, through optogenetic control of either a natural tether—the exocyst complex—or an artificial tether, we report that tethering regulates the mode of fusion. We find that vesicles mainly undergo kiss-and-run instead of full fusion in the absence of functional exocyst. Full fusion is rescued by optogenetically restoring exocyst function, in a manner likely dependent on the stoichiometry of tether engagement with the plasma membrane. In contrast, a passive artificial tether produces mostly kissing events, suggesting that kiss-and-run is the default mode of vesicle fusion. Optogenetic control of tethering further shows that fusion mode has physiological relevance since only full fusion could trigger lamellipodial expansion. These findings demonstrate that active coupling between tethering and fusion is critical for robust membrane merger.

Date: 2021
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DOI: 10.1038/s41467-021-25465-y

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